Since initiation and activation of a chemical or biochemical process requires mixing between reagents, microfluidic systems have much to offer, but a useful microfabricated system should be able to provide not only effective and convenient means to drive and guide liquids in microchannels but also efficient and rapid means to mix them.
Different methods have been proposed to enhance mixing in microfluidic systems, both active and passive. Passive methods are the most attractive since they do not require external energy, while mixing, due to the dominating laminar flow, relies entirely on diffusion or chaotic advection. These methods work by increasing the contact surface and/or decreasing the diffusion path to improve mixing, but the design and manufacture is not always simple and the use of a pump to drive liquids through the channels is in most cases still a need.
Selective wetting is achieved by hydrophilic or hydrophobic patterning of hydrophobic or hydrophilic surfaces, respectively. If two surfaces with mirror image patterns are aligned, separated by a small gap, specific flow paths can be obtained. An aqueous liquid can move driven by capillary forces remaining confined by surface tension between the hydrophilic areas without physical sidewalls. In this way bubble-free, dead-ended flow patterns, as well as chamber filling, can be achieved. This might occur however also when only one of the two surfaces is hydrophilically patterned and the other is entirely hydrophobic, with the advantage to avoid precise alignment. It is important in both cases to choose the dimensions, such as width of the pattern and distance between surfaces, in the allowed range according to the described theories and the experimental data, and the requirement for a pump is thus eliminated.
The combination of passive mixers with capillary pumping is thus preferable but limitations still exist. This might be useful, e.g., to dissolve dry chemistry along the path, but these paths are usually long and the linear velocities small. By taking one step back and using external pumps the process can be speeded up, but controlling the flow path, e.g., introducing a defined volume or stopping the liquid at a defined location and time, can be difficult.
Often, for many useful, real life applications, e.g., in vitro diagnostics assays, reaction kinetics studies, drug- and bio-interaction screening and sample preparation, what is needed is that very small and discrete volumes of reagents are delivered and rapidly mixed into a small reaction chamber or array of chambers, e.g., sub-microliter chambers, which are also preferably detection chambers, thus without further movement of the liquids and without much excess of reagents occupying dead volume or being flushed through the system. Sometimes, especially for reaction kinetics studies, what is required is also a pulsed, well defined start time. Finally, if desired, e.g., as part of sample preparation, the transfer of the small reacted discrete volumes downstream for further processing, should also be easily made possible.
It was already mentioned that surface-directed capillary systems without sidewalls can be used also to fill micro-chambers but the efficient controlled mixing of different small discrete amounts of liquids inside such micro-chambers has not been yet described. In WO 01/52975 A1 a capillary force mixer is disclosed where exactly the opposite concept of efficient mixing is applied, that is the contact surface between two liquids is decreased and the diffusion path is increased.